The invention generally relates to methods of forming vinyl carbonates, particularly those used in forming vinyl carbamates.
Vinyl chloroformate is a monomer used in various applications such as, for example, the making of contact lenses. Currently, it is believed that this compound is only available via a multi-step synthesis involving the use of phosgene and organomercury intermediates. These intermediates are undesirable in that they present heightened environmental concerns. Therefore, it would be desirable to provide a synthetic method which does not necessitate the use of phosgene and organomercury intermediates.
The present invention addresses the above shortcomings and provides methods for making vinyl carbonates and carbamates which do not necessitate the use of phosgene and organomercury intermediates.
In one aspect, the invention provides a method for making a vinyl carbonate represented by the formula (I):
CH2xe2x95x90CHOC(O)X1R1xe2x80x83xe2x80x83(I)
wherein X1 is oxygen or sulfur and R1 is a substituted or an unsubstituted aliphatic alkyl, aryl, aryl alkyl, olefinic, vinyl, or cycloaliphatic group. Preferably, the compound represented by formula (I) is a vinylphenyl carbonate in which instance R1 is a substituted or an unsubstituted aryl group. The method comprises:
(a) reacting a compound represented by formula (II):
X2C(O)X1R1xe2x80x83xe2x80x83(II)
xe2x80x83wherein X2 is a halogen other than fluorine, with a compound represented by formula (III):
M1-Fxe2x80x83xe2x80x83(III)
xe2x80x83wherein M1 is selected from a Group IA metal, in the presence of a first phase transfer catalyst and a first organic solvent, to form a compound represented by formula (IV):
FC(O)X1R1xe2x80x83xe2x80x83(IV)
xe2x80x83and;
(b) reacting a compound represented by formula (IV) with a compound represented by formula (V):
CH2xe2x95x90CHOSi(R2)3xe2x80x83xe2x80x83(V)
xe2x80x83wherein R2 is a substituted or an unsubstituted aliphatic alkyl, aryl, aryl alkyl olefinic, vinyl, or cycloaliphatic group, or any combination thereof, in the presence of a metal salt represented by the formula M2-F wherein M2 is a Group IA metal, a second phase transfer catalyst, and a second organic solvent or solvent combination, to form the compound represented by formula (I).
In a preferred embodiment, the above method further comprises the step of reacting the compound represented by formula (I) with a compound represented by formula (VI):
NHR3R4xe2x80x83xe2x80x83(VI)
wherein R3 and R4 may be the same or different and are selected from a substituted or unsubstituted aliphatic alkyl, aryl, aryl alkyl, olefinic, cycloaliphatic, hydrogen or combinations thereof, to form a compound represented by formula (VII):
R3R4NC(O)OCHxe2x95x90CH2xe2x80x83xe2x80x83(VII).
In another preferred embodiment, the above method further comprises the step of reacting a compound represented by the formula (I) with a compound represented by the formula (VIII):
HOxe2x80x94R5xe2x80x83xe2x80x83(VIII)
wherein R5 is selected from an unsubstituted or substituted aliphatic alkyl, aryl, aryl alkyl, olefinic, or cycloaliphatic group, to form a compound represented by the formula (IX):
R5xe2x80x94Oxe2x80x94C(O)OCHxe2x95x90CH2xe2x80x83xe2x80x83(IX)
In another embodiment, the invention provides a method of forming a carbonate of the formula:
Rxe2x80x2xe2x80x94Oxe2x80x94C(O)xe2x80x94Oxe2x80x94Rxe2x80x2xe2x80x83xe2x80x83(XVI)
wherein Rxe2x80x2 is substituted or unsubstituted alkyl, aryl, aryl alkyl, vinyl, olefinic, or cycloaliphatic group. The method comprises:
reacting a carbonate of the formula (XVII):
Rxe2x80x2xe2x80x94Oxe2x80x94C(O)xe2x80x94Oxe2x80x94Rxe2x80x3xe2x80x83xe2x80x83(XVII)
xe2x80x83wherein Rxe2x80x2 and Rxe2x80x3 are different and are selected from substituted or unsubstituted alkyl, aryl, aryl alkyl, vinyl, olefinic, cycloaliphatic or any non-equivalent combination thereof (i.e., Rxe2x80x2 does not equal Rxe2x80x2), in the presence of: (1) a metal fluoride and a phase transfer catalyst or (2) a quaternary ammonium fluoride species to form the compound of formula (XVI) and a compound of the formula Rxe2x80x3xe2x80x94Oxe2x80x94C(O)ORxe2x80x3.
The invention will now be described with respect to embodiments described herein. It should be appreciated however that these embodiments are for the purposes of illustrating the invention, and are not to be construed as limiting the scope of the invention as defined by the claims.
The foregoing described substituents that can be used in the methods of the invention.
Preferred embodiments of R1, include, without limitation, Øxe2x80x94, p-NO2Øxe2x80x94, p-ClØxe2x80x94, and CH2xe2x95x90CHxe2x80x94. Functional groups and isomers thereof of these embodiments can also be employed.
X1 may be oxygen or sulfur.
X2 is a halogen, preferably one of the halogens chlorine, bromine, or iodine (i.e., other than fluorine).
M1 and M2 are independently selected from one of the Group IA metals, such as, for example, lithium, sodium, potassium, and the like.
R2 may be selected from unsubstituted or substituted aliphatic alkyl, aryl, aryl alkyl, olefinic, vinyl, cycloaliphatic, or any combination thereof.
R5 may be selected from unsubstituted or substituted aliphatic alkyl, aryl, aryl alkyl, olefinic, or cycloaliphatic.
R2 is preferably (CH2)qCH3 wherein q ranges from 0 to 6, and is most preferably CH3 or an aryl group which is most preferably phenyl.
R5 is preferably CH2xe2x95x90C((CH2)pCH3)CO2(CH2)s wherein p ranges from 0 to 6 and is most preferably 0 and s ranges from 1 to 6, and is most preferably 2.
R3 and R4 may be independently selected from unsubstituted or substituted aliphatic alkyl, aryl, aryl alkyl, olefinic, cycloaliphatic, or hydrogen, or any combination thereof. In one preferred embodiment, R3 is hydrogen and R4 is a group represented by the formula:
xe2x80x83(CH2)nSi(OSi((CH2)mCH3)3)3
wherein n ranges from 0 to 6 (preferably is 3) and m ranges from 0 to 6 (preferably is 0).
The first and second phase transfer catalysts may be independently selected from those that are known to one skilled in the art, particularly those employed in disproportionation reactions. For the purposes of the invention, the term xe2x80x9cphase transfer catalystxe2x80x9d is construed to mean any chemical that can assist in the transfer of a reactive species from one phase (e.g., a solid or liquid phase) to another phase in order to facilitate a chemical reaction in this phase.
Exemplary phase transfer catalysts include, without limitation, crown ethers (e.g., 15-crown-5 or 1,4,7,10,13-pentaoxacyclopentadecane, 18-crown-6 or 1,4,7,10,13,16-hexaoxacyclooctadecane, organoammonium salts, and phosphonium salts.
Various organic solvents, such as those employed for the first and second organic solvents (which can be independently selected) can include those which are known to those skilled in the art. Exemplary organic solvents include, for example, polar, aprotic solvents such as, without limitation, dimethyl formamide (xe2x80x9cDMFxe2x80x9d), acetonitrile, dimethyl sulfoxide (xe2x80x9cDMSOxe2x80x9d), and the like. Non-polar organic solvents can also be used such as, without limitation, hexane(s), heptane, toluene, cyclohexane, and the like, along with ether-like solvents such as, but not limited to, diethyl ether, tetrahydrofuran (xe2x80x9cTHFxe2x80x9d), methyl-t-butyl ether (MTBE), the glymes, and the like. Combinations of any of these solvents may be used.
Bases which can be used in the synthesis scheme may include those which are known to one skilled in the art. For example, organic bases may be employed such as, without limitation, 1,8-diazabicyclo[5.4.0. ]undec-7-ene (DBU), triethylamine, N-methylimidazole and the like. Combinations of the above can also be used.
An example of a synthetic scheme for producing vinyl carbonates and vinyl carbamates in accordance with the invention is as follows: 
wherein X1, X2, R1, R2, R3, R4, and R5 are defined hereinabove, and M2 is a Group IA metal such as, for example, sodium or potassium.
A specific embodiment of a synthesis scheme in accordance with the invention is as follows:

Various techniques may be employed for purifying the carbonate and/or carbamate products formed by methods of the invention. Examples of purification techniques include, but are not limited to, wiped film evaporation (WFE), column chromatography (including flash and other pressure types as well as simulated moving bed techniques), selective reactivity, low temperature crystallization and/or trituration, and zone refining. These techniques may be used alone or in combination.
In various embodiments, the compound of formula (VII) may be present in a mixture along with a compound of the formula (XVIII):
ØX1C(O)NR3R4xe2x80x83xe2x80x83(XVIII)
wherein R3 and R4 may be the same or different substituted or unsubstituted alkyl, aryl, aryl alkyl, cycloaliphatic or olefinic group, or a combination thereof, and wherein the aromatic substituent may be substituted or unsubstituted. The compound of formula (XVIII) is often a by-product of the reaction which forms the compound of formula (VII). In such embodiments, the method of the invention may optionally further comprise the step of reacting the compound of formula (XVIII) with a compound of formula (XIX):
HNR6R7xe2x80x83xe2x80x83(XIX)
wherein R6 and R7 are individually selected from hydrogen, a substituted or unsubstituted alkyl, aryl, aryl alkyl, cycloaliphatic or olefinic group, or any combination thereof. The amine selectively reacts with the compound of formula (XVIII) relative to the compound of formula (VII). In one embodiment, the aromatic substituent may be a substituted or unsubstituted aromatic or heteroaromatic, or their corresponding polycyclic analogs, such as, without limitation, phenyl, biphenyl, napthyl, or a polymer bound analog. The amine purification is advantageous in that it may be carried out directly in the same reaction vessel (e.g., pot) that produces the compounds of formulas (XVIII) and (VII) without any intermediate purification or washing steps.
Although not intending to be bound by theory, it is believed that the synthesis path for the selective reaction of the compound of formula (XVIII) may be as follows:
ØX1C(O)NR3R4+HNR6R7xe2x86x92ØOH+R6R7NC(O)NR3R4
2R6R7NC(O)NR3R4xe2x86x92R6R7NC(O)NR6R7+R3R4NC(O)NR3R4
wherein R3, R4, R6 and R7 are defined above.
The above scheme is believed to be advantageous in that selective generation of mixed and symmetrical ureas are more easily separated from the vinyl carbamate of formula (VII) than is the aromatic carbamate of formula (XVIII).
The amine referred to above may be selected from various compounds known to one skilled in the art. Examples of amines include, without limitation, alkyl, heterocyclic, or aromatic amines. Examples of alkyl amines include primary and secondary amines. Specific examples include, without limitation, diethyl amine and ethylene diamine. Other bis-alkyl or aromatic amines can be used. The amine may be preferably used in an amount ranging from about 10 to about 50 mole percent based on the compound of formula (VI).
A number of processing conditions may be employed for selectively reacting the compound of formula (XVIII). In a preferred embodiment, the temperature employed during this method ranges from about 40xc2x0 C. to about 80xc2x0 C. under atmospheric pressure. The reaction time preferably is a minimum of 12 hours, and more preferably ranges from about 24 hours to about 72 hours. Preferably, the reaction proceeds until the compound of formula (XVIII) is substantially or completely reacted. The reaction mixture is thereafter preferably stripped under vacuum and the residue dissolved in a suitable organic solvent (e.g., hexane). Preferably, the solution is given aqueous washes, dried using appropriate materials (e.g., magnesium sulfate), then stripped to an oil under vacuum. The resulting product may then be purified in an appropriate manner if so desired.
In another aspect, the invention provides a method of forming a carbonate of the formula:
xe2x80x83Rxe2x80x2xe2x80x94Oxe2x80x94C(O)xe2x80x94Oxe2x80x94Rxe2x80x2xe2x80x83xe2x80x83(XVI)
wherein Rxe2x80x2 is substituted or unsubstituted alkyl, aryl, aryl alkyl, vinyl, olefinic, or cycloaliphatic group. The method comprises
reacting a carbonate of the formula (XVII):
Rxe2x80x2xe2x80x94Oxe2x80x94C(O)xe2x80x94Oxe2x80x94Rxe2x80x3xe2x80x83xe2x80x83(XVII)
xe2x80x83wherein Rxe2x80x2 and Rxe2x80x3 are different and are selected from substituted or unsubstituted alkyl, aryl, aryl alkyl, vinyl, olefinic, cycloaliphatic or any combination thereof, in the presence of: (1) a metal fluoride and a phase transfer catalyst, or (2) a quaternary ammonium fluoride species to form the compound of formula (XVI). Although not intending to be bound by theory, the above reaction is believed to be a disproportionation reaction.
In one embodiment, the formula (XVI) is represented by the formula (X):
R1R2Cxe2x95x90CR3OC(O)OR3Cxe2x95x90CR1R2xe2x80x83xe2x80x83(X)
wherein R1, R2, and R3 are independently selected from hydrogen, substituted or unsubstituted alkyl, aryl, aryl alkyl, vinyl, olefinic, cycloaliphatic or any combination thereof, and the formula (XVII) is represented by the formula (XI):
R1R2Cxe2x95x90CR3OC(O)OR4xe2x80x83xe2x80x83(XI)
wherein R1, R2, and R3 are defined above, and R4 is selected from substituted or unsubstituted alkyl, aryl, aryl alkyl, vinyl, olefinic, or cycloaliphatic. Preferably, each of R1, R2, and R3 are hydrogen, and R4 is Ø.
Various metal fluorides may be employed in accordance with the invention such as, without limitation, fluorides of Group IA metals such as sodium, potassium, and lithium.
Any of the phase transfer catalysts described hereinabove can be used in the above reaction. Preferably, the phase transfer catalyst is a crown ether, with an exemplary crown ether being 18-crown-6.
Another aspect of the invention provides a method for the formation of a compound of formula (IX) by reacting a compound of formula (VIII) with a compound of formula (XVI) or (XVII). For example, the compound of formula (XVI) or the compound of formula (XVII) can be reacted with the compound of formula (XIV):
HO(CH2)nSi(CH3)2OSi(CH3)2(CH2)mOHxe2x80x83xe2x80x83(XIV)
wherein n ranges from 1 to 10 and m ranges from 1 to 10 to form a compound of formula (XV):
CH2xe2x95x90CHOC(O)O(CH2)nSi(CH3)2OSi(CH3)2(CH2)mOC(O)OCHxe2x95x90CH2xe2x80x83xe2x80x83(XV)
Preferably in this method, the compounds of formula (XVII) and (XVI) are represented by formula (XI) wherein each of R1, R2, and R3 are hydrogen, and R4 is Ø or vinyl.
An embodiment illustrating a general procedure for carrying out the methods of the invention is as follows. Modifications to this procedure may be made without departing from the spirit and scope of the invention. First, a reactant (e.g., chloroformate) is reacted in a polar solvent (e.g., acetonitrile) in a suitable reaction vessel at a specified temperature range (e.g., from about 20xc2x0 C. to about 60xc2x0 C.) with a metal fluoride (e.g., sodium fluoride) for a specified time period (e.g., about 10 to about 30 hours) in the presence of a phase-transfer agent (e.g., a crown ether such as 15-crown-5 for example). In a specific embodiment, the sodium chloride is filtered out, and the fluoroformate is isolated and purified by an acceptable technique (e.g., distillation).
Secondly, a second reactant (e.g., chlorotrialkylsilane) is reacted in a polar solvent (e.g., DMF) in the presence of a high-boiling base (e.g., DBU) with an aldehyde at a specified temperature (e.g., from about 20xc2x0 C. to about 40xc2x0 C.) for a specified time period (e.g., from about 4 to about 8 hours) to produce a product (e.g., a silyl enol ether). The product is isolated by a suitable technique (e.g., partial vacuum distillation), and purified by a suitable technique under appropriate pressure conditions (e.g., fractional distillation at atmospheric pressure).
Thirdly, the above-prepared intermediates are combined in a reaction performed in a solvent mixture composed of a polar and a non-polar solvent in a particular ratio under suitable processing conditions (e.g., at about 20xc2x0 C. to about 60xc2x0 C.) for a specified time period (e.g., about four to about eight hours) in the presence of catalytic amounts of a metal fluoride (e.g., potassium fluoride) and a phase-transfer catalyst (e.g., a crown ether such as 18-crown-6 for example). The metal fluoride is removed by a suitable procedure (e.g., silica gel treatment), and the product is thereafter isolated and purified by a suitable technique (e.g., distillation).
Fourth, the above-prepared vinyl carbonate may be reacted with an appropriate component (e.g., an alcohol or an amine) to yield the corresponding vinyl carbonate or vinyl carbamate. Such a reaction is preferably carried out in an ethereal solvent such as, for example, THF under specified processing conditions (e.g., from about 30xc2x0 C. to about 50xc2x0 C. for 6 to 24 hours). A non-polar solvent such as, for example, hexane may be used to advantage during washes of the reaction product for workup.
Further, in the case of carbamates derived from primary amines, contaminating side-product carbamates may be selectively removed by reaction with another amine as alluded to herein. This reaction is conducted under specified conditions (e.g., from about 40xc2x0 C. to about 80xc2x0 C. for about 24 to about 72 hours) sufficient to convert the non-vinyl carbamate to a symmetrical urea. The urea is typically more easily separated from the vinyl carbamate by common purification methods such as column chromatography than was the original non-vinyl carbamate. The side-product of this reaction is preferably phenol, from the preferred vinyl phenyl carbamate, which is easily removed from the workup via an appropriate technique (e.g., caustic wash).
Finally, symmetrical carbonates may be derived from unsymmetrical precursors by a disproportionation reaction. This reaction is effected by heating the original carbonate in the presence of catalytic amounts of a metal fluoride such as, e.g., potassium fluoride and a phase-transfer catalyst such as, e.g., a crown ether, 18-crown-6 being an example. The lower-boiling symmetrical carbonate is removed from the reaction mixture via an appropriate technique (e.g., fractional distillation) as it is formed, then purified by known techniques, e.g., re-distillation.
Processing aids and/or additives known to one skilled in the art can be used in any of the above reactions if so desired. It should be appreciated that in certain instances the above solvents used in the above reactions may contain water or may be essentially or substantially free of water.